RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Giving bendamustine hydrochloride together with lenalidomide and dexamethasone may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bendamustine hydrochloride and lenalidomide when given together with dexamethasone and to see how well they work in treating patients with relapsed multiple myeloma.

The Maximum Tolerated Dose (MTD) is the dose level below that at which a dose limiting toxicity (DLT) is observed in ≥ 33% (i.e., ≥ 2 of 6) subjects in a cohort. A dose limiting toxicity is defined as one of the following adverse events in the Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 deemed at least possibly related to treatment:

Grade 2 neuropathy with pain

Any grade 3 Non-Hematologic toxicity

Any grade Non-Hematologic event requiring a dose reduction in cycle 1 or delaying the next cycle by >14 days.

Grade 4 neutropenia

Febrile neutropenia

Grade 4 thrombocytopenia

Grade 3 thrombocytopenia associated with bleeding

Any Hematologic event requiring a dose reduction in cycle 1 or a delay in the next cycle of treatment by >14 days.

We are reporting the results of this endpoint as the number of DLTs per dose level.

Patients receive dexamethasone orally or IV on days 1, 8, 15, and 22; bendamustine hydrochloride IV over 30 minutes on days 1 and 2; and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: bendamustine hydrochloride

Given IV

Other Names:

bendamustin hydrochloride

bendamustine

cytostasan hydrochloride

Ribomustin

SDX-105

Treanda

Drug: lenalidomide

Given orally

Other Names:

CC-5013

IMiD-1

Revlimid

Drug: dexamethasone

Given orally or IV

Other Names:

Aeroseb-Dex

Decaderm

Decadron

Decaspray

DM

DXM

Detailed Description:

PRIMARY OBJECTIVES: I. To determine the Maximum Tolerated Dose (MTD) of bendamustine and lenalidomide in combination with dexamethasone in subjects with Multiple Myeloma (MM) in first or second relapse. (Phase I) II. To evaluate the confirmed response rate of bendamustine in combination with lenalidomide and dexamethasone in subjects with MM in first or second relapse. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the safety of bendamustine in combination with lenalidomide and dexamethasone. (Phase I and II) II. To evaluate time-to-tumor-progression, progression-free survival, duration of response, and overall survival. (Phase II) OUTLINE: This is a phase I dose escalation study of bendamustine hydrochloride and lenalidomide followed by a phase II study. Patients receive dexamethasone orally or IV on days 1, 8, 15, and 22; bendamustine hydrochloride IV over 30 minutes on days 1 and 2; and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least stable disease after 6 courses may continue to receive lenalidomide and dexamethasone as above in the absence of disease progression or unacceptable toxicity. Dexamethasone may be discontinued after 12 courses of therapy at the treating investigator's discretion. After completion of study treatment, patients are followed at 4 weeks and then periodically for up to 2 years.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion:

Diagnosis of MM and documentation of at least 1 prior therapy (induction therapy followed by stem cell transplantation is considered one prior therapy) but not more than two previous therapies

Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide

Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

Able to take aspirin (325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA or at high risk of developing thrombosis may use warfarin or low molecular weight heparin)

All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment

Subject has an ECOG =< 2 OR Karnofsky >= 60% performance status; patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible

FCBP must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing

Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. q.d. or its equivalent) for symptom management and comorbid conditions; doses of corticosteroid should be stable for at least 7 days prior to study treatment

Prior radiation therapy within 2 weeks of the first dose of study treatment

Concurrent therapy with a marketed or investigational anticancer therapy

Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient

Other investigational agents are not to be used during the study

Prior peripheral stem cell transplant within 12 weeks of the first dose of study treatment

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01049945